In Vitro and In Vivo Efficacy of Amphotericin B Combined with Posaconazole against Experimental Disseminated Sporotrichosis

We evaluated the combination of posaconazole with amphotericin B in vitro and in a murine model of systemic infections caused by Sporothrix brasiliensis and Sporothrix schenckii sensu stricto. In vitro data demonstrated a synergistic effect, and although posaconazole alone was effective against sporotrichosis, efficacy in terms of survival and burden reduction was increased with the combination. This combination might be an option against disseminated sporotrichosis, especially when itraconazole or amphotericin B at optimal doses are contraindicated.     

Long‐Term Evaluation of Periodontal Parameters and Implant Outcomes in Periodontally Compromised Patients: A Systematic Review

Background : The aim of this systematic review is to evaluate the long‐term outcomes of patients with periodontitis submitted to periodontal therapy/maintenance and implant placement. Methods: Studies reporting clinical and/or long‐term implant outcomes from partially edentulous patients with periodontitis who were treated and followed periodontal maintenance for ≥5 years were considered eligible for the review. Screening of the articles, data extraction, and quality assessment were conducted independently and in duplicate. Results: Search of MEDLINE, EMBASE, and CENTRAL databases resulted in 959 papers, and of them 931 were excluded after title/abstract assessment. The full texts of 28 potentially eligible publications were screened, but only 10 studies met inclusion criteria. Most of the included studies (77.8%) presented a medium/high methodologic quality. The results demonstrated that patients with a diagnosis of periodontitis had satisfactory implant outcomes. Implant survival was high (92.1%) within studies reporting 10 years of follow‐up. Parameters related to probing depth, clinical attachment level, and bone loss around teeth increased the occurrence of peri‐implantitis and implant loss. Non‐attendance to periodontal maintenance and smoking habits were also associated with less favorable implant outcomes. Conclusions: This systematic review confirmed that implant therapy can be successfully used in patients with a diagnosis of periodontitis who underwent proper therapy and regular periodontal maintenance. Residual pockets, non‐attendance to the periodontal maintenance program, and smoking were considered to be negative factors for the long‐term implant outcomes.     

Bone Demineralization With Citric Acid Enhances Adhesion and Spreading of Preosteoblasts

Background: Previous studies have demonstrated that bone demineralization can improve consolidation in bone grafts. The biologic mechanisms underlying this phenomenon remain unclear. Methods: Twelve adult male guinea pigs were used in this experiment. Forty‐five bone samples removed from the calvaria of nine animals were divided in groups (n = 9) according to the time of demineralization with citric acid (50%, pH 1): 15, 30, 90, and 180 seconds and non‐demineralized samples (control). Preosteoblasts (MC3T3‐E1) were cultured on the bone samples for 24, 48, and 72 hours (n = 3). Fifteen samples removed from the remaining three animals were analyzed by scanning electron microcopy/energy dispersive spectrometry (SEM/EDS) after demineralization (n = 3). Results: The number of preosteoblasts increased significantly with time in all groups. The bone surface area covered by these cells increased with time, except in the control group. Intragroup differences occurred between 24 and 72 hours (P <0.05). Samples demineralized for 30 seconds showed greater area covered by preosteoblast cells than for the other times of demineralization in all periods of cell culture (P <0.05) without a statistically significant difference compared with 15 seconds. SEM/EDS showed diminished content of calcium (Ca) after 15 seconds of demineralization, but the Ca content increased after 180 seconds of demineralization (P <0.05). The phosphorus (P) amount increased significantly only after 30 seconds of demineralization (P <0.5). The sulfur (S) content was increased in demineralized samples in relation to non‐demineralized ones, reaching the highest level after 90 seconds, when the difference became significant in relation to all the other times of demineralization (P <0.05). Magnesium (Mg) content did not differ significantly between demineralized and non‐demineralized samples. Conclusions: Bone surfaces demineralized for 30 seconds increased the spreading of preosteoblasts as well as the surface area covered by these cells. Bone demineralization deserves to be studied in periodontal and maxillofacial regenerative procedures.     

Tolerance and physiologic effects of nocturnal mask pressure support vs proportional assist ventilation in chronic ventilatory failure

STUDY OBJECTIVES: To compare the tolerance and physiologic effects of a 5-night treatment with either nasal proportional assist ventilation (PAV) or pressure support ventilation (PSV) in patients with chronic ventilatory failure. DESIGN: Cross-over, randomized, controlled study. SETTING: Rehabilitation units of pneumology department. PATIENTS OR PARTICIPANTS: Four patients with COPD and 10 patients with restrictive thoracic diseases with chronic hypercapnia (median baseline Paco(2), 55.1 mm Hg) were studied. INTERVENTIONS: In a cross-over study, nasal PAV and PSV set at the patient's comfort were randomly applied during 5 consecutive nights (with a 2-night washout period). MEASUREMENTS AND RESULTS: Continuous nocturnal pulse oximetric saturation (Spo(2)) and arterial blood gas results at wake-up were evaluated at baseline during spontaneous breathing and on the fifth day of ventilatory support. Dyspnea, sleep quality, adaptation, and comfort at inspiration and expiration by visual analog scale (VAS) were evaluated every day as well as a side effects score. On the fifth day, there were no significant differences in daytime Paco(2) (median PAV, 53.3 mm Hg; median PSV, 50.2; p = 0.168). Mean nocturnal Spo(2) improved significantly with both PAV and PSV without any significant differences between modes (baseline median, 92%; PAV median, 94.5%; PSV median, 95%). The percentage of the study night spent < 90% Spo(2) (T90) was slightly but significantly higher with PAV than with PSV (median PAV T90, 4%; median PSV T90, 2%; p = 0.049). The VAS symptom score was similar at day 5 between modes; however, nasal and oral dryness were lower (p = 0.05) and alarm noise was higher (p = 0.037) with PAV. CONCLUSIONS: After 5 days of treatment, both modes had similar tolerance, and were equally effective in reducing daytime hypercapnia and improving nocturnal saturation and symptoms. However, PAV induced less nasal and oral dryness but was associated with higher alarm noise.     

Trypsin inhibitor from tamarindus indica L. seeds reduces weight gain and food consumption and increases plasmatic cholecystokinin levels

OBJECTIVES:

Seeds are excellent sources of proteinase inhibitors, some of which may have satietogenic and slimming actions. We evaluated the effect of a trypsin inhibitor from Tamarindus indica L. seeds on weight gain, food consumption and cholecystokinin levels in Wistar rats.

METHODS:

A trypsin inhibitor from Tamarindus was isolated using ammonium sulfate (30–60%) following precipitation with acetone and was further isolated with Trypsin-Sepharose affinity chromatography. Analyses were conducted to assess the in vivo digestibility, food intake, body weight evolution and cholecystokinin levels in Wistar rats. Histological analyses of organs and biochemical analyses of sera were performed.

RESULTS:

The trypsin inhibitor from Tamarindus reduced food consumption, thereby reducing weight gain. The in vivo true digestibility was not significantly different between the control and Tamarindus trypsin inhibitor-treated groups. The trypsin inhibitor from Tamarindus did not cause alterations in biochemical parameters or liver, stomach, intestine or pancreas histology. Rats treated with the trypsin inhibitor showed significantly elevated cholecystokinin levels compared with animals receiving casein or water.

CONCLUSION:

The results indicate that the isolated trypsin inhibitor from Tamarindus reduces weight gain by reducing food consumption, an effect that may be mediated by increased cholecystokinin. Thus, the potential use of this trypsin inhibitor in obesity prevention and/or treatment should be evaluated.     

Biochemical characterization and role of the proteasome in the oxidative stress response of adult Schistosoma mansoni worms

The trematode Schistosoma mansoni, an important parasite of humans, is the principle agent of the disease schistosomiasis. In the human host, one of the most important stress factors of this parasite is the oxidative stress generated by both the metabolism of the worm and the immune system of the host. The proteasomal system is responsible for protein homeostasis during oxidative stress. The 26S proteasome is a multicatalytic protease formed by two compartments, a 20S core and regulatory particle 19S, and controls the degradation of intracellular proteins, hence regulating many cellular processes. In the present report, we describe the biochemical characterization and role of the 20S proteasome in the response of adult S. mansoni worms exposed to hydrogen peroxide. Characterization of the response to the oxidative stress included the evaluation of viability, egg production, mortality, tegument integrity, and both expression and activity of proteasome. We observed decreases in viability, egg production as well as 100 % mortality at the higher concentrations of hydrogen peroxide tested. The main changes observed in the tegument of adult worms were peeling as well as the appearance of bubbles and a decrease of spines on the tubercles. Furthermore, there were increases in 26S activity to the same extent as 20S proteasome activity, although there was increase of 20S proteasome content, suggesting that degradation of protein oxidized in adult worms is due to the 20S proteasome. It was demonstrated that adult S. mansoni worms are sensitive to oxidative stress, and that a variety of processes in this parasite are altered under this condition. The work contributes to a better understanding of the mechanisms employed by S. mansoni to survive under oxidative stress.